Biomedical subjects

D A Larson

Publications and source records attributed to D A Larson.

At least 37 records · Page 2Linked to original sources

PubMed1996

Gamma knife for glioma: selection factors and survival.

PURPOSE: To determine factors associated with survival differences in patients treated with radiosurgery for glioma. METHODS AND MATERIALS: We analyzed 189 patients treated with Gamma Knife radiosurgery for primary or recurrent glioma World Health Organization (WHO) Grades 1-4. RESULTS CONCLUSION: The median minimum tumor dose was 16 Gy (8-30 Gy) and the median tumor volume was 5.9 cc (1.3-52 cc). Brachytherapy selection criteria were satisfied in 65% of patients. Median follow-up of all surviving patients was 65 weeks after radiosurgery. For primary glioblastoma patients, median survival from the date of pathologic diagnosis was 86 weeks if brachytherapy criteria were satisfied and 40 weeks if they were not (p = 0.01), indicating that selection factors strongly influence survival. Multivariate analysis showed that increased survival was associated with five variables: lower pathologic grade, younger age, increased Karnofsky performance status (KPS), smaller tumor volume, and unifocal tumor. Survival was not found to be significantly related to radiosurgical technical parameters (dose, number of isocenters, prescription isodose percent, inhomogeneity) or extent of preradiosurgery surgery. We developed a hazard ratio model that is independent of the technical details of radiosurgery and applied it to reported radiosurgery and brachytherapy series, demonstrating a significant correlation between survival and hazard ratio. CONCLUSIONS: Survival after radiosurgery for glioma is strongly related to five selection variables. Much of the variation in survival reported in previous series can be attributed to differences in distributions of these variables. These variables should be considered in selecting patients for radiosurgery and in the design of future studies.

Adolescent↗

PubMed1996

Reirradiation of primary CNS tumors.

PURPOSE: Primary central nervous system (CNS) tumors are seldom reirradiated due to toxicity concerns and sparse clinical data regarding efficacy. METHODS AND MATERIALS: We retrospectively reviewed 34 patients with primary brain tumors retreated with fractionated external beam irradiation at the University of California, San Francisco from 1977-1993. Tumors included 15 medulloblastomas, 10 high-grade gliomas, 7 low-grade gliomas, and 2 meningiomas. RESULTS: Initial course of radiation was radical in intent for all patients. Median age at initial diagnosis was 19.8 years (range: 3.6-67). Median interval between radiation courses was 16.3 months (range: 3.8-166). Median Karnofsky Performance Status (KPS) prior to reirradiation was 80 (range: 40-100). Reirradiation volumes overlapped previous treatment in 30 patients and were nonoverlapping in 4 patients. Fractionation schemes used were hyperfractionated in 17, conventionally fractionated in 9, and hypofractionated in 8. Cumulative maximum overlap dose within the CNS ranged from 43.2-111 Gy (median: 79.7 Gy). Retreatment was completed as planned in 27 out of 34 patients and modified or aborted in 7 (four tumor progression on retreatment, three patient request). As measured from the time of retreatment median progression free and overall survival was 3.3 and 8.3 months. Clinical and radiographic indices were stabilized or improved in about half of patients evaluable at a median of 3 months postretreatment. Complications (early or late) potentially attributable to retreatment were noted in 10 of 34 (29%) of patients. Overt necrosis was noted in 3 of 34 (9%) of patients and the actuarial risk of necrosis was 22% at 1 year following retreatment. CONCLUSIONS: Reirradiation of primary central nervous system tumors was associated with only modest palliative and survival benefits in this retrospective review. Difficulties separating toxicity due to retreatment vs. tumor progression and limited patient survival following retreatment preclude definite conclusions regarding the safety of this practice.

Adolescent↗

PubMed1996

Radiosurgery for hemangioblastoma: results of a multiinstitutional experience.

PURPOSE: Between June 1988 and June 1994. 38 hemangioblastomas were treated with stereotactic radiosurgery (SR) at three SR centers to evaluate the efficacy and potential toxicity of this therapeutic modality as an adjuvant or alternative treatment to surgical resection. METHODS AND MATERIALS: SR was performed using either a 201-cobalt source unit or a dedicated SR linear accelerator. Of the 18 primary tumors treated, 16 had no prior history of surgical resection and were treated definitively with SR and two primary lesions were subtotally resected and subsequently treated with SR. Twenty lesions were treated with SR after prior surgical failure (17 tumors) or failure after prior surgery and conventional radiotherapy (three tumors). Eight patients were treated with SR for multifocal disease (total, 24 known tumors). SR tumor volumes measured 0.05 to 12 cc (median: 0.97 cc). Minimum tumor doses ranged from 12 to 20 Gy (median: 15.5 Gy). RESULTS: Median follow-up from the time of SR was 24.5 months (range: 6-77 months). The 2-year actuarial over-all survival was 88 +/- 15% (95% confidence interval). Two-year actuarial freedom from progression was 86 +/- 12% (95% confidence interval). The median tumor volume of the lesions that failed to be controlled by SR was 7.85 cc (range: 3.20-10.53 cc) compared to 0.67 cc (range: 0.05-12 cc) for controlled lesions (p - 0.0023). The lesions that failed to be controlled by SR received a median minimum tumor dose of 14 Gy (range: 13-17 Gy) compared to 16 Gy (range: 12-20 Gy) for controlled lesions (p = 0.0239). Seventy-eight percent of the surviving patients remained neurologically stable or clinically improved. There were no significant permanent complications directly attributable to SR. CONCLUSIONS: This report documents the largest experience in the literature of the use of SR in the treatment of hemangioblastoma. We conclude that SR: (a) controls the majority of primary and recurrent hemangioblastomas; (b) offers the ability to treat multiple lesions in a single treatment session, which is particularly important for patients with Von Hippel-Lindau Syndrome; and that (c) better control rates are associated with higher doses and smaller tumor volumes.

Adrenal Cortex Hormones↗

PubMed1996

Demonstration of brachytherapy boost dose-response relationships in glioblastoma multiforme.

PURPOSE: To evaluate brachytherapy dose-response relationships in adults with glioblastoma undergoing temporary 125I implant boost after external beam radiotherapy. METHODS AND MATERIALS: Since June 1987, orthogonal radiographs using a fiducial marker box have been used to verify brain implant source positions and generate dose-volume histograms at the University of California, San Francisco. For adults who underwent brachytherapy boost for glioblastoma from June 1987 through December 1992, tumor volumes were reoutlined to ensure consistency and dose-volume histograms were recalculated. Univariate and multivariate analysis of various patient and treatment parameters were performed evaluating for influence of dose on freedom from local failure (FFLF) and actuarial survival. RESULTS: Of 102 implant boosts, 5 were excluded because computer plans were unavailable. For the remaining 97 patients, analyses with adjustment for known prognostic factors (age, KPS, extent of initial surgical resection) and prognostic factors identified on univariate testing (adjuvant chemotherapy) showed that higher minimum brachytherapy tumor dose was strongly associated with improved FFLF (p = 0.001). A quadratic relationship was found between total biological effective dose and survival, with a trend toward optimal survival probability at 47 Gy minimum brachytherapy tumor dose (corresponding to about 65 Gy to 95% of the tumor volume); survival decreased with lower or higher doses. Two patients expired and one requires hospice care because of brain necrosis after brachytherapy doses > 63 Gy to 95% of the tumor volume with 60 Gy to > 18 cm3 of normal brain. CONCLUSION: Although higher minimum tumor dose was strongly associated with better local control, a brachytherapy boost dose > 50-60 Gy may result in life-threatening necrosis. We recommend careful conformation of the prescription isodose line to the contrast enhancing tumor volume, delivery of a minimum brachytherapy boost dose of 45-50 Gy in conjunction with conventional external beam radiotherapy, and reoperation for symptomatic necrosis.

Adolescent↗

PubMed1996

The effect of setup uncertainties on the radiobiological advantage of fractionation in stereotaxic radiotherapy.

PURPOSE: There may be radiobiological advantages in administering stereotaxic radiation treatment in multiple fractions instead of by a single irradiation. However, a larger planning target volume may be required for fractionated stereotaxic radiotherapy than for a single session treatment, if decreased geometrical precision and increased setup uncertainty are associated with multiple-fraction treatments. This factor may partially offset the radiobiological gain. The purpose of this study is to estimate the potential therapeutic gain of fractionated treatments for brain tumors, and to assess the effect of increased setup uncertainty on the potential gain. METHODS AND MATERIALS: The concept of biologically effective dose (BED), based on the linear quadratic (LQ) model, was used to quantify the therapeutic efficacy of the respective treatment schema. Therapeutic gain (TG) was defined as the ratio of tumor BEDs, for multiple fractions and single treatment, respectively, for the same normal brain BED. To include the effect of increased planning volume in fractionated treatment, a power-law relationship was assumed for the volume dependence of prescription dose, and the TG was recalculated using the "volume-adjusted" doses. RESULTS: The therapeutic gain for fractionated treatment increases with fraction number, and is smaller for larger single treatment doses. For example, in going from 1 to 10 fractions, the TG is 1.40, 1.32, or 1.27 for single treatment dose of 20, 30, or 40 Gy, respectively. Also, the TG is more significant for the initial few fractions. The benefit of fractionation is diminished if larger planning volume is needed for multiple fraction treatments. For example, the above TG are reduced to 1.19, 1.11, or 1.06, if a 2 cm planning target volume in single fraction treatment is enlarged to 2.3 cm in fractionated treatment. CONCLUSION: Consideration of the therapeutic gain with fractionation should include estimates of setup uncertainty for multiple-fraction treatments, relative to that of single fraction radiosurgery.

Brain Neoplasms↗

PubMed1996

Bromodeoxyuridine labeling index in glioblastoma multiforme: relation to radiation response, age, and survival.

PURPOSE: Various measures of the rate of tumor cell proliferation have been found to predict survival in patients with intracerebral gliomas. We correlated the bromodeoxyuridine labeling index (BrdUrd LI) with the response to radiation therapy, survival, and known prognostic factors in a series of patients with glioblastoma multiforme (GM) to test its utility as a prognostic factor. METHODS AND MATERIALS: The BrdUrd LI was determined in 200 newly diagnosed intracranial GMs. Age and sex were known for all patients. The response to radiation therapy was determined in 116 patients by comparing neuroimaging studies obtained before and after external beam radiation therapy. Survival was analyzed in 64 patients who were treated according to two consecutive prospective clinical protocols. RESULTS: The median BrdUrd LI was 6.5% (mean, 7.2%; range, 1.1-25.4%). The BrdUrd LI did not correlate significantly with age, sex, radiation response, or survival. Age and Karnofsky performance score were independent prognostic factors in our cohort. CONCLUSION: The proliferative rate as measured by BrdUrd LI was not a prognostic factor in our GM cohort. The BrdUrd LI did not correlate significantly with known prognostic factors in GM. There was no significant relationship between BrdUrd LI and radiation response.

Adolescent↗

PubMed1996

Stereotactic radiosurgery for malignant melanoma to the brain.

This article offers support for using radiosurgery in the treatment of patients with melanoma brain metastases. Although patients with multiple metastases may fare somewhat worse than patients with single metastases, the difference is not statistically significant. The only significant prognostic factor that we were able to identify was smaller total target volume (favorable factor), although further study with longer follow-up and more patients may reveal other factors. Radiosurgery is appealing to patients and physicians because it is noninvasive and requires minimal hospitalization and recovery. Gamma Knife therapy offers patients a rapid method for achieving local control, which may be particularly important for patients who would otherwise be considered for specific protocols (such as some using IL-2) which preclude enrollment unless intracranial disease is controlled. We conclude that stereotactic radiosurgery is an effective treatment modality, with acceptable toxicity, for patients with either solitary or multiple melanoma metastases to the brain.

Adolescent↗

PubMed1996

Gamma knife radiosurgery in children.

52 pediatric patients were treated with radiosurgery at the University of California, San Francisco. Arteriovenous malformations were treated in 27 patients. Complete obliteration was noted in 4 of 12 patients imaged more than 2 years after radiosurgery. Arteriovenous malformation rebleed was noted in 1 patient. Symptomatic T2 changes were noted in 2 patients. Among 29 neoplasms treated in 25 patients, local control was noted in 5 of 7 low-grade gliomas, 5 of 14 high-grade gliomas, 4 of 5 craniopharyngiomas and 3 of 3 sarcomas. Three patients treated for neoplasms developed necrosis after radiosurgery.

Adolescent↗

PubMed1996

Long-term follow-up after high-activity 125I brachytherapy for pediatric brain tumors.

A retrospective review including long-term follow-up (4.6-12.0 years) was performed of all 28 pediatric patients who underwent high-activity 125I brachytherapy at the University of California, San Francisco, for primary or recurrent brain tumors from 1980 until 1991. There were 4 glioblastomas, 11 high-grade nonglioblastoma multiforme (NGM) malignant gliomas, 10 contrast-enhancing low-grade NGM, 2 choroid plexus carcinomas, and 1 rhabdomyosarcoma. The 13 survivors included 7 of 8 patients with primary high-grade NGM, 2 of 3 patients with primary low-grade NGM, and 3 of 7 patients with recurrent low-grade NGM. Necrosis (with or without tumor) was identified in 17 of 22 reoperated patients. The mean Karnofsky performance status was 88 +/- 9 at the time of brachytherapy, 87 +/- 7 at 3 years, and 87 +/- 9 in 11 patients alive at 6-12 years. Brachytherapy is a useful modality for treating selected pediatric brain tumors, and although focal necrosis is a common sequela, it does not tend to have a major impact on the Karnofsky performance status, if the implant site is amenable to reoperation.

Adolescent↗

PubMed1996

Radiation response and survival time in patients with glioblastoma multiforme.

The determine the value of radiographically assessed response to radiation therapy as a predictor of survival in patients with glioblastoma multiforme (GBM), the authors studied a cohort of 301 patients who were initially treated according to uniform clinical protocols. All patients had newly diagnosed supratentorial GBM and underwent the maximum safe resection followed by external- beam radiation treatment (60 Gy in standard daily fractions or 70.4 Gy in twice-daily fractions of 160 cGy). The radiation response and survival rates were assessable in 222 patients. The extent of resection and the immediate response to radiation therapy were highly correlated with survival, both in a univariate analysis and after correction for age and Karnofsky performance scale (KPS) score in a multivariate Cox model (p< 0.001 for radiation response and p=0.04 for extent of resection). A subgroup analysis suggested that neuroimaging obtained within 3 days after surgery served as a better baseline for assessment of radiation response than images obtained later. Imaging obtained within 3 days after completion of a course of radiation therapy also provided valid radiation response scores. The impact of the radiographically assessed radiation response on survival time was comparable to that of age or KPS score. This information is easily obtained early in the course of the disease, may be of value for individual patients, and may also have implications for the design and analysis of trials of adjuvant therapy for GBM, including volume-dependent therapies such as radiosurgery or brachytherapy.

Adolescent↗

PubMed1996

Interstitial brachytherapy for intracranial metastases.

In large medical centers, the availability of radiosurgery has relegated brachytherapy to a lesser role in the treatment of newly diagnosed solitary brain metastases. However, the treatment planning in radiosurgery is complex, and in some case the hardware is prohibitively expensive; low or high dose rate brachytherapy requires only a stereotactic frame, commercially available software, and encapsulated radionuclides or newer tiny linear accelerators. Interstitial brachytherapy also remains an option for the treatment of recurrent solitary metastases when other forms of treatment have failed. This article reviews the radiobiology of low and high dose rate interstitial brachytherapy, the University of California San Francisco (UCSF) results using iodine-125 implants, and early experience with the photon radiosurgery system (PRS) at Massachusetts General Hospital for the treatment of brain metastases.

Adolescent↗

PubMed1996

Radiotherapy for cerebral metastases.

Whole brain radiotherapy (WBRT) for patients with unresected brain metastases results in symptomatic response in about 50% of patients and improvement in median survival to 3 to 6 months. Most patients with brain metastases are appropriately treated with a conventional palliative course of 30 Gy in 10 fractions over 2 weeks, although accelerated hyperfractionation with 32 Gy to the whole brain plus a boost to at least 54.4 Gy at 1.6 Gy twice daily yields better results for patients with solitary metastases. Patients with a life-expectancy of greater than 6 months should receive at most that or equal to 2.0 Gy per fraction to minimize the risk of radiation-induced leukoencephalopathy and dementia. Patients with good performance status, absent or controlled primary tumor, and no extracranial metastases might benefit from surgical resection or radiosurgery (with or without adjunctive WBRT) to improve local control.

Brain Neoplasms↗

PubMed1995

Medulloblastoma in adults.

PURPOSE: To examine the relationship between extent of disease and outcome in adults with medulloblastoma. METHODS AND MATERIALS: We reviewed the records of all patients over 15 years old with newly diagnosed or recurrent medulloblastoma treated by or referred to the University of California, San Francisco, and recorded demographic characteristics, clinical symptoms, radiographic findings, extent of resection, staging, myelography, computerized tomography (CT) scans or magnetic resonance (MR) images of the spine, histopathological assessment, treatment received, treatment response, recurrence patterns, and survival duration. RESULTS: A total of 47 patients were identified, 26 of whom were designated "poor-risk" because they had < 75% removal of tumor, metastatic disease, or brain-stem or leptomeningeal invasion. All patients had radiation therapy; 32 had adjuvant chemotherapy. Twenty-two patients (47%) died of tumor progression, 19 are progression-free, and 6 are alive with disease. The median survival time was 282 weeks in poor-risk patients and has not been reached in good-risk patients. Overall and disease-free 5-year survival rates differed significantly between the two groups (81% vs. 54%, p = 0.03 and 58% vs. 38%, p = 0.05, respectively). Tumors most often recurred in the posterior fossa. The median survival time from recurrence was 77 weeks (range 44 to 89 weeks). CONCLUSION: These findings are similar to those reported for children. Therefore, staging and treatment in adults should be approached the same way as in children: staging should include cerebrospinal fluid assessment and spinal imaging. Treatment should be based on staging, and should include craniospinal irradiation; additional chemotherapy should probably be reserved for poor-risk patients.

Adolescent↗

PubMed1995

Radiation therapy for primary intracranial germ-cell tumors.

PURPOSE: To evaluate the diagnosis, therapy, and survival of patients with intracranial germ-cell tumors. To define the role of prophylactic craniospinal irradiation and chemotherapy necessary to impact on survival. METHODS AND MATERIALS: Forty-eight patients with surgically confirmed or suspected primary intracranial germ-cell tumors treated at UCSF between 1968-1990 were reviewed. Thirty-four patients had a pathologic diagnosis, including 24 germinomas, 3 malignant teratomas, 2 choriocarcinomas, 1 embryonal carcinoma, 1 endodermal sinus tumor, and 3 mixed tumors. Information obtained included histology, location, cerebrospinal fluid (CSF) cytology, alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin (B-HCG), metastatic evaluation, radiation details, survival, and sites of failure. Minimum follow-up time was 2 years and ranged to a maximum of 24 years, with a median of 8 years. RESULTS: Median age at diagnosis was 16 years with 36 males and 12 females. Ten of 32 patients had elevated B-HCG at diagnosis; 6 of 29 had elevations of AFP. Cerebrospinal fluid cytology was negative in 35 of 36 patients evaluated; myelography or spinal MRI was positive in only 1 of 31 patients studied. Five-year actuarial disease-free survival after irradiation was 91% for germinomas, 63% for unbiopsied tumors, and 60% for nongerminoma germ-cell tumors with doses of 50-54 Gy to the local tumor site with or without whole-brain or whole-ventricular irradiation. Routine prophylactic cranio-spinal axis irradiation was not given with a spinal only failure rate of 2%. Eleven of 48 patients have expired, with an actuarial 5-year survival rate of 100% for germinomas, 79% for nonbiopsied tumors, and 80% for nongerminoma germ-cell tumors. CONCLUSION: With complete diagnostic craniospinal evaluation, spinal irradiation is not necessary. Cure rates for germinomas are excellent with irradiation alone. Multidrug chemotherapy is necessary with irradiation for nongerminoma germ-cell tumors. Histology is the most important prognostic factor; therefore, all patients should have surgical conformation of their diagnosis so that appropriate treatment can be given.

Adolescent↗

PubMed1995

The treatment of brain stem and thalamic gliomas with 78 Gy of hyperfractionated radiation therapy.

PURPOSE: To see whether increasing the dose of hyperfractionated radiation therapy from 72 to 78 Gy would increase survival time in patients with gliomas, particularly those with brain stem or thalamic tumors. METHODS: Seventy-eight patients with a clinical and radiographic diagnosis of a brain stem or thalamic glioma were enrolled in a trial to receive 78 Gy (1.0 Gy twice a day). Six patients with disease in other sites were also treated. The initial response to therapy was determined by comparing pretreatment magnetic resonance images and neurological examinations with those obtained within 2 weeks of completing therapy; subsequent responses were determined from bimonthly follow-up images. Time-to-tumor progression was measured from the date radiation therapy began until the date of documented radiographic or clinical progression. Survival time was measured from the date radiation therapy began until the date of death. Cox proportional hazards analysis was used to estimate the effects of specific variables on survival. RESULTS: Of 81 evaluable patients, 68 received > or = 76 Gy, 10 received between 70 and 75 Gy, and 3 received between 60 and 68 Gy. The overall response or stabilization rate was 70.4%. Tumor size decreased in 30.8% of patients; 39.5% had stable disease, and 29.6% had immediate progression. The median survival time was 12.7 months (16.1 months for adults and 10.8 months for children). The median time to tumor progression was 9.0 months (11.4 months for adults and 8.4 months for children). A duration of symptoms < or = 2 months and a diffuse lesion were each associated with shorter survival and progression times. CONCLUSIONS: For patients with brain stem or thalamic gliomas, increasing the dose of radiation therapy from 72 to 78 Gy did not significantly improve survival. Different treatment strategies are clearly needed.

Adolescent↗

PubMed1995

Radiosurgery patterns of practice.

We distributed a questionnaire on radiosurgery patterns of practice to members of the International Stereotactic Radiosurgery Society (ISRS). Responses were obtained from physicians at 52 facilities, who had treated more than 13,000 patients. Most respondents were found to work within a multidisciplinary team, and averaged 17.3 specialist-hours devoted per patient on the day of radiosurgery. These results will enable radiosurgeons to determine if their practice differs from the norm and to adjust their practice standards, if appropriate.

Central Nervous System Diseases↗

PubMed1995

Sarcomas subsequent to cranial irradiation.

The development of sarcoma subsequent to cranial irradiation is a rare but serious and potentially fatal event. We describe seven patients who had undergone cranial irradiation (range, 1600-6000 cGy) to treat their primary disease and who developed sarcomas within the irradiated field. The median time from radiation therapy to the development of a sarcoma was 8 years (range, 4 to 15 yr). Fibrosarcomas developed in four patients, and malignant fibrous histiocytomas developed in three. Despite aggressive treatment, the prognosis was poor; the median survival from the diagnosis of sarcoma was 19 months. Sarcoma should be considered in the differential diagnosis of a new lesion or a lesion that progresses several years after radiation therapy.

Adolescent↗

PubMed1995

Large effect of age on the survival of patients with glioblastoma treated with radiotherapy and brachytherapy boost.

A retrospective review was undertaken to study the influence of age on the survival of patients undergoing brachytherapy boost for glioblastoma multiforme. From February 1981 through December 1992, 159 adults with primary glioblastoma multiforme underwent high-activity iodine-125 brain implant boost after external beam radiotherapy. There were 98 men and 61 women, ranging in age from 18 to 73 years (median, 52 yr). Karnofsky performance scores ranged from 70 to 100 (median, 90). Surgery before radiotherapy consisted of biopsy in 7% of patients, subtotal resection in 66%, and gross total resection in 27%. External beam radiotherapy doses ranged from 39.6 to 76.8 Gy, with 91% of patients receiving 59.4 to 61.2 Gy. Brachytherapy doses ranged from 35.7 to 66.5 Gy (median, 55.0 Gy) at 0.30 to 0.70 Gy per hour (median, 0.43 Gy/h). Reoperations were performed in 81 patients (51%). Information on quality of life was available for 13 of the 14 living 3-year survivors; 10 patients were steroid independent, and mean Karnofsky performance scores had decreased from 92 at the time of brachytherapy to 75 at the last follow-up. Univariate and multivariate analyses showed that age was the most important parameter influencing survival (P < 0.0005). The nine patients 18 to 29.9 years old had a 3-year survival probability of 78 +/- 14% (median survival was not yet reached at the time of this report), with a follow-up of 145 to 511 weeks in living patients (median, 322 wk).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗